Abstract
BackgroundIn clinical applications of CAR T-cell therapy, life-threatening adverse events including cytokine release syndrome and neurotoxicity can lead to treatment failure. Outcomes of patients treated with anti-CD30 CAR T- cell have been disappointing in relapsing/refractory (r/r) classical Hodgkin’s Lymphoma (cHL).MethodsIn order to understand the applicable population of multiple CAR T-cell therapy, we examined the expression of CD19, CD20, and CD30 by immunohistochemistry (IHC) in 38 paraffin-embedded specimens of cHL. In the past two years, we found only one patient with cHL who is eligible for combined anti-CD19 and CD30 CAR T-cell treatment. This patient’s baseline characteristics were prone to severe adverse events. We treated this patient with low doses and multiple infusions of anti-CD19 and CD30 CAR T-cell.ResultsThe positive expression of CD19+ + CD30+ in Reed-Sternberg (RS) cells is approximately 5.2% (2/38). The patient we treated with combined anti-CD19 and CD30 CAR T-cell did not experience severe adverse events related to CAR T-cell therapy and received long term progression-free survival (PFS).ConclusionFor high risk r/r cHL patients, low doses of CAR T-cell used over different days at different times might be safe and effective. More clinical trials are warranted for CD19 and CD30 CAR T-cell combination therapy.
Highlights
Classical Hodgkin’s Lymphoma can be cured using standard chemotherapy with or without radiation [1]
We recruited patients with Classical Hodgkin’s Lymphoma (cHL) for this phase I/II single-center clinical trial that met the following inclusion criteria: 1) 18 to 75 years old with CD19+ and CD30+ r/r lymphoma confirmed by IHC staining; 2) Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less; 3) measurable lesion ≥1 cm; 4) previous treatment with at least 2 systemic chemotherapy regimens concluded at least 4 weeks prior; 5) no autologous stem cell transplantation (ASCT) within 12 weeks; and 6) passing the expert panel discussion
Among the 38 paraffin-embedded cHL specimens, only 2 (5.2%) specimens showed positive CD19 staining in RS cells, including 1 mixed cellularity Hodgkin’s lymphoma and 1 unknown case
Summary
Classical Hodgkin’s Lymphoma (cHL) can be cured using standard chemotherapy with or without radiation [1]. The prognosis for patients with cHL that are relapsing/refractory (r/r) after first-line treatment or autologous stem cell transplantation (ASCT) is very poor [3]. Besides CD30, some B cells antigens, such as CD19 and CD20, have been identified in cHL [6]. CD30 is very lowly expressed in normal tissues, it is selectively overexpressed in RS cells, rendering this antigen a promising target for novel treatment strategy [3]. In clinical applications of CAR T-cell therapy, life-threatening adverse events including cytokine release syndrome and neurotoxicity can lead to treatment failure. Outcomes of patients treated with anti-CD30 CAR T- cell have been disappointing in relapsing/refractory (r/r) classical Hodgkin’s Lymphoma (cHL)
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